A hitchhiker's guide to survival finally makes CENs

Abstract

Most strains of the yeast Saccharomyces cerevisiae contain many copies of a 2-microm plasmid, a selfish autonomously replicating DNA that relies on two different mechanisms to ensure its survival. One of these mechanisms involves the high fidelity segregation of the plasmids to daughter cells during cell division, a property that is starkly reminiscent of centromeres. A new study reported in this issue (see Hajra et al. on p. 779) demonstrates that this high fidelity is achieved by the 2-microm plasmid, effectively recruiting the centromeric histone Cse4 from its host yeast cell to forge its own centromere and finally revealing how the 2-microm plasmid has survived in budding yeasts over millions of years.

Figure 1.

Two modes of recruiting Cse4. (A) Yeast chromosomal centromeres (CENs) are 125 bp and contain highly homologous CDE I and III sequences and a CDE II (86–98% adenosine-thymidine rich) that are the same length but are variable in sequence across all centromeres. The CBF3 complex proteins bind to the CDE III element and help recruit Cse4 to assemble a single Cse4 nucleosome most likely at CDE II. For simplicity, only the CBF3 complex and Mif2 are shown. (B) The STB loci of 2-μm plasmids consist of proximal STB repeats (each repeat is ∼60% adenosine-thymidine rich and 125 bp in length) and a distal STB element that acts as a transcriptional silencer and is important for STB function. No CBF3 complex proteins are known to localize to STB, and Cse4 recruitment at STB is independent of Ndc10 function. Instead, this recruitment relies on the plasmid-encoded Rep1 and Rep2 proteins and the RSC2 chromatin remodeling complex.

Figure 2.

CEN and STB evolve very differently. (A) The 16 S. cerevisiae centromeres share many highly conserved features with each other and with the eight centromeres of Kluyveromyces lactis, indicating a high degree of sequence constraint, especially in CDE III. (B) Two types of 2-μm plasmids have been found in S. cerevisiae. Type I plasmids are quite similar to each other in size and sequence but are only 70% identical in sequence to type II plasmids, which also have a high degree of length variation that appears to bear functional consequences for 2-μm partitioning.